Preparation and characterization of full-spectrum cannabis extract loaded poly(thioether-ester) nanoparticles: In vitro evaluation of their antitumoral efficacy

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Δ9 -tetrahydrocannabinol (THC), cannabidiol (CBD) and other natural compounds produced by Cannabis sativa exhibit a wide array of therapeutic effects on the human body. As a result, extracts containing controlled amounts of different cannabinoids, called full spectrum extracts, have generated great interest and are currently being assayed for the management of many diseases including cancer. However, cannabinoids exhibit limited bioavailability due to their low solubility in water and moderate stability. Therefore, developing novel methods of cannabinoid administration or encapsulation that could help to improve the efficacy of treatments based on the use of these compounds is an issue of great interest. The purpose of this study was to develop biobased poly (thioether-ester)-PTEe nanoparticles containing full-spectrum Cannabis extract-CN and assay their potential efficacy in vitro cancer models. To do this we used two different approaches: 1) in-situ thiol-ene miniemulsion polymerization (Me-PTEe) and 2) thiol-ene miniemulsification/solvent evaporation method using PTEe synthesized previously by thiol-ene bulk polymerization (Se-PTEe). In both cases an α,ω-diene-diester monomer assembled from derivatives of castor oil was used. We found that CN-PTEe nanoparticles presented a high encapsulation efficiency with an average diameter of between 91 and 229 nm. Likewise, CN-PTEe nanoparticles reduced the viability to a similar extent as free CN of the cancer cell lines (B16F10, T98, and U87) but not of the non-tumoral NIH3T3 cells. Furthermore, treatment with CN-PTEe nanoparticles mimicked the working mechanism of non-encapsulated cannabinoids (inhibited the AKT signaling pathway and induced autophagy) in BF16F10 melanoma cells. These observations support the idea that the PTEe nanoparticles are effective CN nanocarriers and that they could be assayed in future studies to investigate their potential anticancer activity.